KEGG   PATHWAY: mcep04137
Entry
mcep04137                   Pathway                                
Name
Mitophagy - animal - Mugil cephalus (flathead mullet)
Description
Mitochondria act as the energy powerhouse of the cell, and are essential for eukaryotic cells to grow and function normally. However, deleterious byproducts of oxidative phosphorylation process called reactive oxidative species (ROS) lead to mitochondrial dysfunction. If the damage is too excessive to be repaired, such mitochondria are selectively recognized and targeted for degradation by a specific mode of autophagy, termed mitophagy. The loss of the mitochondrial membrane potential can induce mitophagy, involving the kinase PINK1 and the E3 ligase Parkin. PINK1 serves as the sensor for the mitochondrial depolarization and recruits Parkin, followed by ubiquitin-dependent recruitment of mitophagy receptors. There are also several PINK1/Parkin-independent mitophagy pathways, in which a group of LIR-containing receptors are required in response to different stimuli. Mitophagy contributes to the maintenance of a healthy mitochondrial network and the prevention of programmed cell death.
Class
Cellular Processes; Transport and catabolism
Pathway map
mcep04137  Mitophagy - animal
mcep04137

Other DBs
GO: 0000422
Organism
Mugil cephalus (flathead mullet) [GN:mcep]
Gene
124996033  huwe1; E3 ubiquitin-protein ligase HUWE1 isoform X1 [KO:K10592] [EC:2.3.2.26]
124996426  traf2b; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
124996543  zgc:73226; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [KO:K15464]
124996632  ulk1b; serine/threonine-protein kinase ULK1 isoform X1 [KO:K21357] [EC:2.7.11.1]
124996821  bnip3lb; BCL2 interacting protein 3 like B [KO:K15465]
124996826  junE; JunE proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
124996991  marchf5l; E3 ubiquitin-protein ligase MARCHF5 [KO:K10660] [EC:2.3.2.27]
124997018  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
124997163  [KO:K03173] [EC:2.3.2.27]
124997541  zgc:55558; GTPase KRas [KO:K07827]
124997719  rab5c; ras-related protein Rab-5C [KO:K07889]
124997973  nbr1b; next to BRCA1 gene 1 protein isoform X1 [KO:K17987]
124997987  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
124998068  atf4b; activating transcription factor 4b [KO:K04374]
124998153  smurf2; E3 ubiquitin-protein ligase SMURF2 [KO:K04678] [EC:2.3.2.26]
124998158  fis1; mitochondrial fission 1 protein [KO:K17969]
124998299  tbc1d17; TBC1 domain family member 17 [KO:K19945]
124998489  rraS; ras-related protein R-Ras [KO:K07830]
124998774  eif2s1b; eukaryotic translation initiation factor 2 subunit 1b [KO:K03237]
124999354  foxo3b; forkhead box protein O3B [KO:K09408]
124999845  [KO:K21343] [EC:3.4.19.12]
124999889  optN; optineurin [KO:K19946]
124999924  samm50l; sorting and assembly machinery component 50 homolog B [KO:K07277]
124999953  zgc:136908; transitional endoplasmic reticulum ATPase isoform X1 [KO:K13525]
125000296  tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
125000985  [KO:K17986]
125003580  tomm20b; mitochondrial import receptor subunit TOM20 homolog B [KO:K17770]
125003825  [KO:K04678] [EC:2.3.2.26]
125003859  atf4a; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374]
125004202  rhot1b; mitochondrial Rho GTPase 1b isoform X1 [KO:K07870] [EC:3.6.5.-]
125004907  [KO:K10636] [EC:2.3.2.36]
125005365  rras2; ras-related protein R-Ras2 [KO:K07830]
125005651  usp8; ubiquitin carboxyl-terminal hydrolase 8 isoform X1 [KO:K11839] [EC:3.4.19.12]
125005695  [KO:K08341]
125005927  [KO:K03097] [EC:2.7.11.1]
125006057  mitfa; melanocyte inducing transcription factor a isoform X1 [KO:K09455]
125006195  sp1; transcription factor Sp1 [KO:K04684]
125006279  [KO:K03097] [EC:2.7.11.1]
125006431  si:dkey-13a21.4; ras-related protein rab7 [KO:K07897]
125006492  map1lc3a; microtubule-associated proteins 1A/1B light chain 3A [KO:K10435]
125006633  [KO:K07897]
125006659  tfe3b; transcription factor E3b isoform X1 [KO:K09105]
125006668  [KO:K05704] [EC:2.7.10.2]
125006727  tfeB; transcription factor EB isoform X1 [KO:K15590]
125006775  [KO:K07897]
125007092  mon1a; vacuolar fusion protein MON1 homolog A [KO:K20195]
125007337  [KO:K04570]
125007354  mon1bb; vacuolar fusion protein MON1 homolog B isoform X1 [KO:K20195]
125007811  sqstm1; sequestosome-1 [KO:K14381]
125008186  map1lc3cl; microtubule-associated proteins 1A/1B light chain 3C [KO:K10435]
125008712  mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
125009211  tfe3a; transcription factor E3a [KO:K09105]
125009241  opa1; dynamin-like 120 kDa protein, mitochondrial isoform X1 [KO:K17079] [EC:3.6.5.5]
125009396  mfn1b; mitofusin-1b [KO:K21356] [EC:3.6.5.-]
125009453  jun; transcription factor AP-1 [KO:K04448]
125009480  tomm70a; mitochondrial import receptor subunit TOM70 [KO:K17768]
125009506  uba52; ubiquitin-60S ribosomal protein L40 [KO:K02927]
125009756  fkbp8; peptidyl-prolyl cis-trans isomerase FKBP8 [KO:K09574] [EC:5.2.1.8]
125010254  [KO:K04451]
125010340  [KO:K04448]
125010614  [KO:K17081]
125010757  mul1a; mitochondrial ubiquitin ligase activator of nfkb 1-A [KO:K15688] [EC:2.3.2.27]
125010912  relA; transcription factor P65 [KO:K04735]
125011160  [KO:K15688] [EC:2.3.2.27]
125011251  atg9b; autophagy-related protein 9B [KO:K17907]
125011371  mfn1a; mitofusin-1 isoform X1 [KO:K21356] [EC:3.6.5.-]
125011593  [KO:K20131]
125011644  ulk1a; serine/threonine-protein kinase ULK1a isoform X1 [KO:K21357] [EC:2.7.11.1]
125012059  [KO:K13525]
125012155  usp30; ubiquitin carboxyl-terminal hydrolase 30 isoform X1 [KO:K11851] [EC:3.4.19.12]
125012559  bnip3la; BCL2 interacting protein 3 like A [KO:K15465]
125012645  mtx3; metaxin-3 isoform X1 [KO:K17776]
125012733  [KO:K03173] [EC:2.3.2.27]
125012891  pgam5; serine/threonine-protein phosphatase PGAM5, mitochondrial isoform X1 [KO:K15637] [EC:3.1.3.16]
125013081  [KO:K20131]
125013288  src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
125013444  hif1al; hypoxia inducible factor 1 subunit alpha, like isoform X1 [KO:K08268]
125013701  nlrx1; NLR family member X1 [KO:K12653]
125013910  [KO:K09455]
125014305  samm50; sorting and assembly machinery component 50 homolog A [KO:K07277]
125014334  fkbp16; FKBP prolyl isomerase 16 [KO:K09574] [EC:5.2.1.8]
125014514  siah1; E3 ubiquitin-protein ligase Siah1 isoform X1 [KO:K04506] [EC:2.3.2.27]
125014660  kraS; GTPase KRas [KO:K07827]
125014878  ambra1b; activating molecule in BECN1-regulated autophagy protein 1B [KO:K17985]
125014935  map1lc3b; microtubule-associated proteins 1A/1B light chain 3B [KO:K10435]
125015016  [KO:K02833]
125015087  [KO:K08341]
125015301  tbc1d15; TBC1 domain family member 15 [KO:K20168]
125015378  bcl2l13; bcl-2-like protein 13 isoform X1 [KO:K15485]
125015412  arih1; E3 ubiquitin-protein ligase arih1 [KO:K11968] [EC:2.3.2.31]
125015556  csnk2a2b; casein kinase II subunit alpha' [KO:K03097] [EC:2.7.11.1]
125015685  [KO:K17776]
125015914  [KO:K03097] [EC:2.7.11.1]
125015918  [KO:K03115]
125016125  tax1bp1b; tax1-binding protein 1 homolog B isoform X1 [KO:K21347]
125016284  zgc:92606; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
125016640  rab5ab; RAB5A, member RAS oncogene family, B [KO:K07887]
125016948  tomm40; mitochondrial import receptor subunit TOM40 homolog [KO:K11518]
125017501  rab5b; ras-related protein Rab-5B [KO:K07888]
125017617  mrasa; ras-related protein M-Ras [KO:K07831]
125018130  fundc1; FUN14 domain-containing protein 1 [KO:K17986]
125018329  mtx2; metaxin-2 [KO:K17776]
125018473  marchf5; E3 ubiquitin-protein ligase MARCH5 [KO:K10660] [EC:2.3.2.27]
125018520  rps27a; ubiquitin-40S ribosomal protein S27a [KO:K02977]
125018694  bnip4; BCL2 interacting protein 4 [KO:K15464]
125018888  prkN; E3 ubiquitin-protein ligase parkin [KO:K04556] [EC:2.3.2.31]
125018940  tomm20a; translocase of outer mitochondrial membrane 20 [KO:K17770]
125019044  bcl2l1; bcl-2-like protein 1 [KO:K04570]
125019343  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125019416  tomm7; mitochondrial import receptor subunit TOM7 homolog [KO:K17771]
125019542  [KO:K04451]
125019568  [KO:K04451]
125019584  [KO:K04451]
125019682  [KO:K08341]
125019807  rab5aa; RAB5A, member RAS oncogene family, A [KO:K07887]
125020061  tax1bp1a; tax1-binding protein 1 homolog A [KO:K21347]
125020246  csnk2b; casein kinase II subunit beta [KO:K03115]
125020566  tomm40l; mitochondrial import receptor subunit TOM40B [KO:K11518]
125020609  foxo6b; forkhead box protein O6b [KO:K09408]
125020826  ubb; LOW QUALITY PROTEIN: polyubiquitin-B [KO:K08770]
125021081  rabgef1; rab5 GDP/GTP exchange factor isoform X1 [KO:K20131]
125021233  e2f1; transcription factor E2F1 [KO:K17454]
125021293  si:dkey-71l1.1; mitochondrial import receptor subunit TOM40B [KO:K11518]
125022122  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125022187  nbr1a; NBR1 autophagy cargo receptor a isoform X1 [KO:K17987]
125022276  becn1; beclin-1 [KO:K08334]
125022293  epas1a; endothelial PAS domain-containing protein 1 [KO:K08268]
125022343  pink1; serine/threonine-protein kinase PINK1, mitochondrial [KO:K05688] [EC:2.7.11.1]
125022465  [KO:K21348]
125022705  ccz1; vacuolar fusion protein CCZ1 homolog [KO:K27045]
125022721  [KO:K07889]
125022740  rhot2; mitochondrial Rho GTPase 2 [KO:K07871] [EC:3.6.5.-]
125022949  mfn2; mitofusin-2 [KO:K06030] [EC:3.6.5.-]
125023245  atg9a; autophagy-related protein 9A [KO:K17907]
125023263  hif1aa; hypoxia inducible factor 1 subunit alpha A [KO:K08268]
125023797  eif2ak3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
125023871  foxo3a; forkhead box protein O3a [KO:K09408]
125024236  mul1b; mitochondrial ubiquitin ligase activator of NFKB 1 [KO:K15688] [EC:2.3.2.27]
Compound
C00035  GDP
C00044  GTP
Reference
PMID:25611507
  Authors
Pickrell AM, Youle RJ
  Title
The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease.
  Journal
Neuron 85:257-73 (2015)
DOI:10.1016/j.neuron.2014.12.007
Reference
PMID:25995186
  Authors
Durcan TM, Fon EA
  Title
The three 'P's of mitophagy: PARKIN, PINK1, and post-translational modifications.
  Journal
Genes Dev 29:989-99 (2015)
DOI:10.1101/gad.262758.115
Reference
PMID:25999423
  Authors
Shirihai OS, Song M, Dorn GW 2nd
  Title
How mitochondrial dynamism orchestrates mitophagy.
  Journal
Circ Res 116:1835-49 (2015)
DOI:10.1161/CIRCRESAHA.116.306374
Reference
PMID:26611876
  Authors
Hamacher-Brady A, Brady NR
  Title
Mitophagy programs: mechanisms and physiological implications of mitochondrial targeting by autophagy.
  Journal
Cell Mol Life Sci 73:775-95 (2016)
DOI:10.1007/s00018-015-2087-8
Reference
PMID:26882551
  Authors
Yamano K, Matsuda N, Tanaka K
  Title
The ubiquitin signal and autophagy: an orchestrated dance leading to mitochondrial degradation.
  Journal
EMBO Rep 17:300-16 (2016)
DOI:10.15252/embr.201541486
Reference
PMID:27021519
  Authors
Yamaguchi O, Murakawa T, Nishida K, Otsu K
  Title
Receptor-mediated mitophagy.
  Journal
J Mol Cell Cardiol 95:50-6 (2016)
DOI:10.1016/j.yjmcc.2016.03.010
Reference
PMID:27443527
  Authors
Roberts RF, Tang MY, Fon EA, Durcan TM
  Title
Defending the mitochondria: The pathways of mitophagy and mitochondrial-derived vesicles.
  Journal
Int J Biochem Cell Biol 79:427-436 (2016)
DOI:10.1016/j.biocel.2016.07.020
Reference
PMID:27701735
  Authors
Arena G, Valente EM
  Title
PINK1 in the limelight: multiple functions of an eclectic protein in human health and disease.
  Journal
J Pathol 241:251-263 (2017)
DOI:10.1002/path.4815
Related
pathway
mcep04140  Autophagy - animal
mcep04210  Apoptosis
KO pathway
ko04137   

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